ABSTRACT PCNSL (primary central nervous system lymphoma) is an aggressive primary brain tumor characterized by the perivascular accumulation of malignant cells that have lymphoid characteristics. It is currently accepted as a unique extranodal non-Hodgkin's lymphoma (NHL). The molecular pathogenesis of PCNSL is not known. PTPRK protein, a regulator of growth factor receptor-mediated phosphorylation that maps to gene locus 6q22-23, may act as a tumor suppressor in PCNSL. Two recent projects by our group suggested that 1. In one Mayo-based project deletion of 6q22-23/PTPRK correlated with shorter patient survival seemingly independent of other cytogenetic abnormalities, treatment time trends, or patient age. 2. In a second SEER Registry-based project Black Americans and White Americans appeared to have significantly differing incidence and survival rates suggesting a genetic factor. We propose to confirm these observations in a population-based setting by interrogating PCNSL specimens from the Iowa, LA County and Hawaii SEER Discard Repositories. We will interrogate these tissues to determine the frequency of deletion of 6q22-23, and in particular deletion of the tumor suppressor gene PTPRK;to determine the association between PTPRK deletions and PTPRK protein expression;and, lastly, to correlate these data with the richly annotated SEER data that includes incidence and survival. The primary focus of this application is etiologic cancer research. Our preliminary data suggests a basis for more extended research. The R03 mechanism was selected to validate observations made in clinical specimens from an NCI-supported resource as a prelude to more detailed investigation. This is a first step in an investigative cascade that will explore racial and genetic influences on PCNSL tumorigenesis.